FI64367C - OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE - Google Patents
OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE Download PDFInfo
- Publication number
- FI64367C FI64367C FI800556A FI800556A FI64367C FI 64367 C FI64367 C FI 64367C FI 800556 A FI800556 A FI 800556A FI 800556 A FI800556 A FI 800556A FI 64367 C FI64367 C FI 64367C
- Authority
- FI
- Finland
- Prior art keywords
- prazosinhydrochloride
- prazosin
- prazosin hydrochloride
- hydrochloride
- water
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
___L—Ί Γβ, KUULUTUSjULKAISU___ L — Ί Γβ, ANNOUNCEMENT
[Β] 11 UTLÄGGNINGSSKRIFT 64367 (45) (51) Kv.lk.^lm.Cl.3 C 07 D 405/12 SUOM | FI N LAN D (21) P«»nttlh»kemus — PstentsnsBknlng 800556 (22) HskemtspilvS — AnsSknlngsdsg 26. 02.80 (FI) (23) AlkupVvi — GHtighetsdsg 26.02.80 (41) Tullut Julkiseksi — Bllvlt offerrtttg 27.08. 8l ja rekifterlhalMtu* N«h«v«k,.p»non j. kuuLjulkalsun pvm.—[Β] 11 UTLÄGGNINGSSKRIFT 64367 (45) (51) Kv.lk. ^ lm.Cl.3 C 07 D 405/12 FINLAND | FI N LAN D (21) P «» nttlh »kemus - PstentsnsBknlng 800556 (22) HskemtspilvS - AnsSknlngsdsg 26. 02.80 (FI) (23) AlkupVvi - GHtighetsdsg 26.02.80 (41) Become Public - Bllvlt offerrtttg 27.08. 8l and rekifterlhalMtu * N «h« v «k, .p» non j. Date of month
Patent- och regi*ter*tyrel»en ' Ansektn utlagd oeh utl.skrKten publlcsrad 29.07-83 (32)(33)(31) pyydetty etuoikeus—Begird prlorltet (71) Orion-yhtymä Oy, Lääketehdas Orion, PL 19, 00101 Helsinki 10, Suomi-Finlar.ö (FI) (72) Pekka Kairisalo, Helsinki, Heinrich Thaler, Espoo, Erkki Juhani Horkanen, Helsinki, Suomi-Finland(Fl) (5^) Pratsosiinihydrokloridin ^-muodon valmistusmenetelmä - Förfarande för framställning av Oi-form av prazosinhydrokloridPatented and registered office of the Ansektn utlagd oeh utl.skrKten publlcsrad 29.07-83 (32) (33) (31) requested privilege — Begird prlorltet (71) Orion Corporation Ltd, Lääketehdas Orion, PO Box 19, FI-00101 Helsinki 10, Finland-Finlar.ö (FI) (72) Pekka Kairisalo, Helsinki, Heinrich Thaler, Espoo, Erkki Juhani Horkanen, Helsinki, Finland-Finland (Fl) (5 ^) Method for the preparation of the ^ form of prazosin hydrochloride - Förfarande för framställning av O-form of prazosin hydrochloride
Keksintö koskee pratsosiinin 1. 2-^4- (2-furoyyli) piperaifsin-1-yyli]-4-amino-6,7-dimetoksikinatsoliinin (kaava I) hydro-kloridin α-muodon uutta valmistusmenetelmää.The invention relates to a new process for the preparation of the α-form of prazosin 1. 2- [4- (2-furoyl) piperazin-1-yl] -4-amino-6,7-dimethoxyquinazoline (formula I) hydrochloride.
H.CQ. .N. J N -CO-s' 0vv '®2 α-muotoa valmistetaan keksinnönmukaisesti siten, että pratsosiinihydrokloridin hydraatista poistetaan kidevesi atseotrooppisella tislauksella dikloorimetaanin avulla.H.CQ. .OF. The α-form of J N -CO-s '0vv' ®2 is prepared according to the invention by removing water of crystallisation from prazosin hydrochloride hydrate by azeotropic distillation with dichloromethane.
Kun kaikki vesi on poistettu, jää jäljelle puhdas pratsosiinihydrokloridin a-muoto.When all the water has been removed, pure form α of prazosin hydrochloride remains.
6436764367
Pratsosiini on tunnettu verenpainetta alentava lääkeaine. Patentissa FI 62082 on karakterisoitu sen vedettömän hydrokloridin eräs kidemuoto ja nimitetty se α-pratsosiinihydrokioridiksi. α-muodolla on esitetty olevan eräitä etuja muihin kidemuotoihin nähden (kts. patentti FI 62082 s. 13). Kyseisestä julkaisusta on lisäksi tunnettua valmistaa α-muotoa kuumentamalla eräitä muita kidemuotoja korkeassa lämpötilassa (100...200°) jossain orgaanisessa liuottimessa, erityisesti 5...7 hiiliatomia sisältävässä alkoholissa.Prazosin is a known antihypertensive drug. FI 62082 characterizes a crystalline form of its anhydrous hydrochloride and names it α-prazosin hydrochloride. The α-form has been shown to have some advantages over other crystal forms (see patent FI 62082 p. 13). It is also known from this publication to prepare the α-form by heating some other crystalline forms at high temperature (100 to 200 °) in an organic solvent, in particular an alcohol having 5 to 7 carbon atoms.
Patentissa FI 62082 esitetyssä α-muodon valmistusmenetelmässä on eräitä haittoja. Pratsosiinihydrokloridi liukenee jonkin verran mainittuihin alkoholeihin, mikä vähentää saantoa. Menetelmän korkeimmilla lämpötila-alueilla (n. 180...200°C) on lisäksi mahdollista, että pratsosiini jo osittain hajoaa. On myös vaarana, että α-muodon sijasta saadaankin γ-muodoksi nimitettyä kiteistä polymorfia (kts. patentti FI 62032 s. 5), ellei keittoaika tai lämpötila ole ollut riittävä. Lisäksi korkealla kiehuvien liuottimien poistaminen tuotteesta voi olla hankalaa.The process for the preparation of the α-form disclosed in patent FI 62082 has some drawbacks. Prazosin hydrochloride is somewhat soluble in said alcohols, which reduces the yield. In addition, at the highest temperature ranges of the process (approx. 180 ... 200 ° C) it is possible that prazosin is already partially degraded. There is also a risk that a crystalline polymorph called γ-form can be obtained instead of the α-form (see patent FI 62032 p. 5), if the cooking time or temperature has not been sufficient. In addition, removing high-boiling solvents from the product can be tricky.
Yllättäen havaittiin, että puhdasta pratsosiinihydrokloridin α-muotoa voidaan valmistaa kvantitatiivisella saannolla ja hyvin yksinkertaisesti siten, että pratsosiinihydrokloridin hydraatista tai vesipitoisesta hydraatista poistetaan vesi atseotrooppisella tislauksella dikloorimetaanin kanssa ja erotetaan vapautuva vesi vedenerotinta käyttäen. Tällöin todettiin muodostuvan yksinomaan pratsosiinihydrokloridin α-muotoa. Tuote identifioitiin iR-spektrinsä perusteella.Surprisingly, it was found that the pure form α of prazosin hydrochloride can be prepared in quantitative yield and very simply by dewatering prazosin hydrochloride hydrate or aqueous hydrate by azeotropic distillation with dichloromethane and separating the liberated water using a water separator. In this case, only the α-form of prazosin hydrochloride was found to be formed. The product was identified by its iR spectrum.
Keksinnönmukainen menetelmä on edullinen ennen kaikkea matalan lämpötilansa (n. 42°) vuoksi. Lisäetuna on se, että dikloorimetaani on huokea, helposti regeneroitavissa oleva ja teollisuuskäyttöön erittäin sopiva liuotin. Epäpuhtauksia ei ole havaittu keksinnönmukaisessa menetelmässä muodostuvan.The method according to the invention is advantageous above all because of its low temperature (about 42 °). An additional advantage is that dichloromethane is an inexpensive, easily regenerable solvent and very suitable for industrial use. No impurities have been found to form in the process of the invention.
il 64367il 64367
Seuraavat esimerkit havainnollistavat keksintöä.The following examples illustrate the invention.
Esimerkki 1.Example 1.
Lietetään 228 g (0,5 mol) pratsosiinihydrokloridin dihydraat-tia (valmistettu patenttihakemuksessa FI 79 0320 esitetyllä menetelmällä) 2200 mlraan dikloorimetaania. Reaktioastiaan liitetään vedenerotin ja seosta keitetään palauttaen, kunnes vettä ei enää erotu (n. 4...6 h). Sakka suodatetaan ja jäljelle jäänyt dikloorimetaani haihdutetaan alennetussa paineessa. Saadaan 210 g (100 % teoreettisesta) pratsosiini-hydrokloridia (haj.p. 280...82°, IR (KBr): 3319, 3226, 3077, 2857, 1634, 1597, 1481, 1468, 1425, 1280, 794, 763, 751, 721, 717, 675 cm ^). IR-spektri on identtinen patentissa FI 62082 kuvatun α-muodon spektrin kanssa.228 g (0.5 mol) of prazosin hydrochloride dihydrate (prepared by the method described in patent application FI 79 0320) are slurried in 2200 ml of dichloromethane. A water separator is connected to the reaction vessel and the mixture is boiled under reflux until no more water separates (about 4 ... 6 h). The precipitate is filtered off and the residual dichloromethane is evaporated off under reduced pressure. 210 g (100% of theory) of prazosin hydrochloride are obtained (dec. 280-82 °, IR (KBr): 3319, 3226, 3077, 2857, 1634, 1597, 1481, 1468, 1425, 1280, 794, 763, 751, 721, 717, 675 cm -1). The IR spectrum is identical to the spectrum of the α-form described in patent FI 62082.
Esimerkki 2.Example 2.
Lietetään 300 g kuivaamatonta vesipitoisesta väliaineesta suodatettua ja vedellä pestyä pratsosiinihydrokloridia (sis. 30 % vettä määritettynä Karl Fischerin menetelmällä) 2200 ml:aan dikloorimetaania ja menetellään esimerkissä 1 esitetyllä tavalla. Saadaan 210 g (100 % teoreettisesta) a-pratsosiinihydrokloridia.Slurry 300 g of prazosin hydrochloride (including 30% water as determined by the Karl Fischer method) filtered from the dry aqueous medium and washed with water in 2200 ml of dichloromethane and proceed as described in Example 1. 210 g (100% of theory) of α-prazosin hydrochloride are obtained.
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI800556A FI64367C (en) | 1980-02-26 | 1980-02-26 | OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE |
| PT72511A PT72511B (en) | 1980-02-26 | 1981-02-16 | Process for the preparation of the alpha-form of prazosin hydrochloride |
| CS811167A CS216226B2 (en) | 1980-02-26 | 1981-02-18 | Method of making the forms of hydrochloride 2-+l 4-+l2-furoyl+p-piperazin-1-yl+p-4-amino-6,7-dimethoxychinazoline |
| NO810590A NO154461C (en) | 1980-02-26 | 1981-02-20 | PROCEDURE FOR PREPARING THE AAA FORM OF HYDROCHLORIDE OF PRAZOSIN 1 OR 2- (4- (2-FUROYL) -PIPERAZIN-1-YL) -4-AMINO-6,7-DIMETOXYKINAZOLINE. |
| DD81227817A DD156532A5 (en) | 1980-02-26 | 1981-02-23 | PROCESS FOR PREPARING THE ALPHA FORM OF PRAZOSINE HYDROCHLORIDE |
| ES499796A ES8201577A1 (en) | 1980-02-26 | 1981-02-25 | A procedure for the preparation of form a of prazosin hydrochloride. (Machine-translation by Google Translate, not legally binding) |
| DK084581A DK157548C (en) | 1980-02-26 | 1981-02-25 | PROCEDURE FOR PREPARING THE CRYSTALLINIC ALFA FORM OF THE HYDROCHLORIDE OF PRAZOSINCHLORIDE |
| PL1981229865A PL128350B1 (en) | 1980-02-26 | 1981-02-25 | Process for preparing alpha-prasosine hydrochloride |
| SU813247560A SU980621A3 (en) | 1980-02-26 | 1981-02-25 | Process for producing alpha-form of prazosine hydrochloride |
| HU81460A HU182297B (en) | 1980-02-26 | 1981-02-25 | Process for producing alpha-modification of prazosine-hydrochloride |
| SE8101265A SE431873B (en) | 1980-02-26 | 1981-02-26 | PROCEDURE FOR PREPARING ALFA FORM OF PRAZOSINE HYDROCHLORIDE |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI800556 | 1980-02-26 | ||
| FI800556A FI64367C (en) | 1980-02-26 | 1980-02-26 | OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI800556A FI800556A (en) | 1981-08-27 |
| FI64367B FI64367B (en) | 1983-07-29 |
| FI64367C true FI64367C (en) | 1986-08-05 |
Family
ID=8513276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI800556A FI64367C (en) | 1980-02-26 | 1980-02-26 | OIL FRAMSTAELLNING AV ALFA FORM AV PRAZOSINHYDROCHLORIDE |
Country Status (11)
| Country | Link |
|---|---|
| CS (1) | CS216226B2 (en) |
| DD (1) | DD156532A5 (en) |
| DK (1) | DK157548C (en) |
| ES (1) | ES8201577A1 (en) |
| FI (1) | FI64367C (en) |
| HU (1) | HU182297B (en) |
| NO (1) | NO154461C (en) |
| PL (1) | PL128350B1 (en) |
| PT (1) | PT72511B (en) |
| SE (1) | SE431873B (en) |
| SU (1) | SU980621A3 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI79107C (en) * | 1984-06-25 | 1989-11-10 | Orion Yhtymae Oy | Process for the preparation of stable form of prazosin hydrochloride. |
-
1980
- 1980-02-26 FI FI800556A patent/FI64367C/en not_active IP Right Cessation
-
1981
- 1981-02-16 PT PT72511A patent/PT72511B/en not_active IP Right Cessation
- 1981-02-18 CS CS811167A patent/CS216226B2/en unknown
- 1981-02-20 NO NO810590A patent/NO154461C/en unknown
- 1981-02-23 DD DD81227817A patent/DD156532A5/en not_active IP Right Cessation
- 1981-02-25 DK DK084581A patent/DK157548C/en not_active IP Right Cessation
- 1981-02-25 ES ES499796A patent/ES8201577A1/en not_active Expired
- 1981-02-25 HU HU81460A patent/HU182297B/en not_active IP Right Cessation
- 1981-02-25 SU SU813247560A patent/SU980621A3/en active
- 1981-02-25 PL PL1981229865A patent/PL128350B1/en unknown
- 1981-02-26 SE SE8101265A patent/SE431873B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO154461C (en) | 1986-09-24 |
| PT72511A (en) | 1981-03-01 |
| DK84581A (en) | 1981-08-27 |
| DD156532A5 (en) | 1982-09-01 |
| SE8101265L (en) | 1981-08-27 |
| SU980621A3 (en) | 1982-12-07 |
| CS216226B2 (en) | 1982-10-29 |
| ES499796A0 (en) | 1981-12-16 |
| PT72511B (en) | 1983-02-01 |
| NO810590L (en) | 1981-08-27 |
| ES8201577A1 (en) | 1981-12-16 |
| FI64367B (en) | 1983-07-29 |
| HU182297B (en) | 1983-12-28 |
| PL229865A1 (en) | 1981-10-30 |
| DK157548B (en) | 1990-01-22 |
| SE431873B (en) | 1984-03-05 |
| PL128350B1 (en) | 1984-01-31 |
| NO154461B (en) | 1986-06-16 |
| FI800556A (en) | 1981-08-27 |
| DK157548C (en) | 1990-06-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: ORION-YHTYMAE OY |